The skin is a complex structure that functions as a barrier to ingress of foreign substances into the body. Molecules moving from the environment into and through an intact skin must first penetrate the stratum corneum, which acts as highly resistant lipid barrier to penetration of these molecules into the skin. In both the pharmaceutical and cosmetic fields, significant efforts have been put forth in attempts to overcome the barrier of the stratum corneum in order to deliver topically functional agents into the skin. Generally, three primary routes across the stratum corneum are available for molecular transport: (1) Normal or chemically modified skin allows diffusion of small molecules, usually following a tortuous intercellular path within the lipids of the stratum corneum; (2) “Shunt” pathways through the hair follicles and sweat ducts may be utilized during iontophoresis, pressure-mediated delivery, and liposomal transport; and (3) Transcellular pathways crossing both the cells and intercellular lipids of the stratum corneum can be created by electroporation to allow passage of chemical compounds
The technique of iontophoresis is in wide use in the administration of drugs as it effectively delivers electrically charged medicaments through the skin and into the capillary structure and lymphatic system. This technique avoids the gastrointestinal side effects sometimes associated with orally ingested drugs and is preferable to subcutaneous or intramuscular injection because of its relatively benign and painless nature.
Although the iontophoresis has been found to be effective, it is also known to be accompanied by a number of undesirable side effects, such as the occurrence of skin injury in the form of iontophoretic burns and irritation in the treated area as well as the formation of undesirable vesicles and bullae on the skin in the treated area. Various complicated methods for preventing these iontophoretic burns have been developed. However, such methods and apparatus have generally been found not to be adequately effective. Consequently, iontophoretic treatments have usually been limited to relatively low electrical currents and relatively short periods of administration.
Iontophoretic drug delivery systems have also been primarily limited to delivering a drug of only a single polarity at a time to a given area, at relatively low concentrations, and have not been suitable for simultaneous delivery of multiple drugs.
The other technique, electroporation, facilitates the transdermal or intradermal delivery of uncharged substances by electrically inducing the formation of transient dermal micropores that allow mobilization of the uncharged substances by diffusion. However, electroporation generally does not produce pores of sufficient diameter to allow passage of large molecules.
Iontophoresis as well as electroporation have been incorporated into many transdermal delivery devices including dermal patches and bioelectrodes. For example, there are many dermal patches known today that incorporate a power source and electrical circuitry for facilitating transdermal delivery. However, these iontophoretic dermal patches and bioelectrodes are often expensive and must be handled by a clinician.
Electrotransport or iontophoretic drug delivery devices have been disclosed as being useful for the delivery of many types of drugs for which it is anticipated that transdermal delivery would be advantageous. U.S. Pat. Nos. 6,169,920 and 6,317,629 to Alza, for example, disclose iontophoretic drug delivery apparatus, and U.S. Pat. Nos. 5,983,130 and 6,718,201 to Alza discloses an electrotransport agent delivery method and apparatus mostly suitable for charged but also for uncharged drugs.
U.S. Pat. Nos. 5,885,211; 6,022,316; 6,142,939; 6,173,202; and 6,527,716 to Eppstein et al., describe devices and methods for forming micropores in the stratum corneum by heating tissue-bound water above the vapor point with a heat conducting element so as to enhance transdermal transport of an analyte or active substance. Additional enhancement techniques include the use of sonic energy, pressure, and chemical enhancers.
Electrosurgery techniques have been used to contract collagen fibers in soft tissue. These techniques typically involve the application of radio frequency (RF) energy to soft collagen tissue to contract and restrict the tissue elasticity. U.S. Pat. No. 6,159,194 to Eggers et al., describes electrosurgical apparatus and methods for inducing tissue contraction while limiting the thermal damage to tissue adjacent to and underlying the treatment site.
U.S. Pat. No. 6,148,232 to Avrahami, which is incorporated herein by reference, describes a device for ablating the stratum corneum of a subject. The device includes a plurality of electrodes, which are applied at respective points on skin of a subject. A power source applies electrical energy between two or more of the electrodes to cause ablation of distinct regions of the stratum corneum (SC), primarily beneath the respective electrodes, and to generate micro-channels. Various techniques for limiting ablation to the stratum corneum are described, including spacing of the electrodes and monitoring the electrical resistance of skin between adjacent electrodes. U.S. Pat. Nos. 6,597,946; 6,611,706; 6,708,060; and 6,711,435 to Avrahami, all assigned to the applicant of the present application and incorporated herein by reference, disclose additional devices for ablating the stratum corneum and generating micro-channels so as to facilitate transdermal passage of substances through the skin. The devices are aimed at reducing sensation and minimizing damage to skin underlying the stratum corneum during micro-channel generation.
WO 2004/039426; WO 2004/039427; and WO 2004/039428, all assigned to the applicant of the present application and incorporated herein by reference, disclose systems and methods for transdermal delivery of pharmaceutical agents. Specifically disclosed are hydrophilic anti-emetic agents, therapeutic agents from patches comprising dried compositions, and pharmaceutical compositions comprising water-insoluble drugs and carrier molecules, which enhance the solubility of the drugs in aqueous solutions.
There is still a recognized need for, and it would be highly advantageous to have a system and methods for efficient intradermal or transdermal delivery of cosmetic agents, which enhance the penetration of the cosmetic agents into skin and increase their bioavailability. As many chemical agents useful for treating skin conditions have limited efficacy due to their poor solubility in aqueous-based cosmetic compositions or to significant oxidation, and as skin is a barrier normally impermeable to water soluble or hydrophilic agents, there is still an unmet need for a system and methods for administering cosmetic agents, which system and methods overcome the major drawbacks of the presently known treatments and improve dramatically the efficacy of cosmetic agents.